Valproic acid attenuates lipopolysaccharide-induced acute lung injury in mice

Inflammation. 2013 Dec;36(6):1453-9. doi: 10.1007/s10753-013-9686-z.


Valproic acid (VPA) has been shown to exert anti-inflammatory and antioxidant effects in a range of diseases including septic shock. However, the effects of VPA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. We found that VPA pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the downregulated nuclear factor kappa B (NF-κB) p65, nitric oxide, and inducible nitric oxide synthase in the lung tissues and the decreased levels of tumor necrosis factor alpha and interleukin-1β in the bronchoalveolar lavage fluid. Furthermore, VPA reduced the nuclear histone deacetylase (HDAC)3 expression whereas increased the cytoplasmic HDAC3 expression. Our results suggested that VPA attenuates the LPS-induced ALI via inhibiting the NF-κB activation probably through a mechanism depending on HDAC3 redistribution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / therapeutic use
  • Bronchoalveolar Lavage Fluid
  • Down-Regulation
  • Histone Deacetylases / biosynthesis
  • Histone Deacetylases / metabolism*
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Interleukin-1beta / biosynthesis
  • Lipopolysaccharides
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / drug effects
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / biosynthesis
  • Peroxidase / metabolism
  • Sepsis / drug therapy
  • Transcription Factor RelA / biosynthesis
  • Transcription Factor RelA / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Valproic Acid / therapeutic use*


  • Anti-Inflammatory Agents
  • Antioxidants
  • Interleukin-1beta
  • Lipopolysaccharides
  • Rela protein, mouse
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Valproic Acid
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Histone Deacetylases
  • histone deacetylase 3